HIPAA COMPLIANT VERSION FOR SITES IN UNITED STATES
Consent for Participation in a Clinical Research Study
Trial to Assess Chelation Therapy (TACT): Grant # 1 U01 AT001156-01
Study Sponsors: National Institutes of Health (NCCAM and NHLBI)
YOU ARE ASKED TO READ THE FOLLOWING FORM TO MAKE SURE THAT YOU
COMPLETELY UNDERSTAND WHAT WILL HAPPEN IF YOU AGREE TO TAKE PART
IN THIS RESEARCH STUDY. SIGNING THIS FORM MEANS THAT THE STUDY
HAS BEEN EXPLAINED TO YOU AND THAT YOU GIVE YOUR PERMISSION TO
TAKE PART. THE FEDERAL GOVERNMENT REQUIRES YOUR APPROVAL IN
WRITING BEFORE YOU TAKE PART IN ANY RESEARCH STUDY. IT IS
IMPORTANT THAT YOU KNOW WHAT WILL TAKE PLACE AND WHAT RISKS ARE
INVOLVED BEFORE YOU DECIDE WHETHER OR NOT TO TAKE PART IN THIS
You are being asked to take part in a research study to test the effectiveness of chelation therapy for patients who have survived a heart attack. The study will involve 1950 patients like you at up to 150 clinical centers. Your participation in this 5-year study will include up to 28 months of intravenous infusions and oral treatments (pills), followed by up to 32 additional months of follow-up and additional pills.
Purpose of the Study
The purpose of this study is to determine the effectiveness of chelation therapy for patients who have survived a heart attack.
Chelation therapy, as used in this study, consists of 40 treatments through a vein in your arm (infusion) of a solution of vitamins and dissolved materials that are thought to bind specific toxic elements circulating in your blood. These elements, known as heavy metals, include iron, copper, and calcium, and may contribute to the development of heart disease. The Food and Drug Administration has approved chelation therapy for treatment of lead poisoning, but not as a treatment for heart disease. Chelation therapy has been practiced in the community for many years. The present clinical practice of chelation therapy also involves the use of high-dose antioxidant vitamins, minerals, and nutritional supplements taken by mouth. However, like with chelation therapy, there is no evidence that these supplements are beneficial for patients like you. The Trial to
Assess Chelation Therapy (TACT) will test chelation solution versus a placebo (a substance with no active ingredient) salt-water solution, and high-dose vitamins and minerals taken by mouth versus placebo vitamins. All patients will also receive a low-dose vitamin.
If you agree to take part in this study, you will be scheduled for a screening visit. During this visit, a complete medical history and a simple physical examination will be performed. We will also obtain samples of your blood (two tablespoonfuls) to check your blood cell counts as well as your kidney and liver function. You will be asked questions about how you rate your health, about your activities, how you are feeling emotionally and some questions about your working status, education, and income. We expect this screening visit to take about 90 minutes to carry out. Once the laboratory tests are complete, you will be contacted by the research staff and told whether you are eligible, and, if so, asked to schedule your first infusion visit.
Also, at the screening visit, you will be asked to fill out a Confidential Patient Information Form. This form will ask for specific information such as your name, address, phone number, social security number, and other identifiers that will be entered confidentially by the Study Coordinator. The information will be used by the research staff and the Economics and Quality of Life Coordinating Center at the Duke Clinical Research Institute to follow your care and check for changes in your health.
The research staff will call for a treatment assignment and you will be assigned randomly by a computer (by chance, like flipping a coin) to one of these four groups:
Chelation solution Chelation placebo Chelation solution Chelation placebo
+ + + +
High-dose High-dose High-dose High-dose
supplements* Supplements* Supplement Supplement
*All patients take low-dose supplements during infusion period only.
All patients, including yourself, will receive a total of 40 infusions, beginning with one infusion per week for 30 weeks, followed by an additional 10 infusions given approximately once every 2 weeks to once every 2 months. It will take up to 28 months to complete all the required infusions. Each infusion consists of receiving the solution slowly through a needle in your vein. The needle will be inserted by trained medical personnel under sterile conditions and each infusion will last for a minimum of 3 hours. You will have blood drawn for laboratory tests during 10
of your visits. Each time, you will have approximately 1 tablespoonful of blood drawn. During each visit, you will be asked how you feel, and whether you have had any complaints or other problems. In addition, the research staff will ask you whether you have had any new heart problems or hospitalizations, and will measure your blood pressure and perform a simple physical exam. Because of the time of the infusions, you should count on being at the clinic for at least 5 hours. If you live far away from your doctor’s office, you may spend a lot of time traveling back and forth.
If you are assigned to the chelation group you will receive a standard intravenous mixture established by the American College for Advancement in Medicine.
The components are as follows. Please review the list of components carefully and notify us if you have an allergy to any of them:
Additive Role of Additive
Up to 3 grams of EDTA Chelating agent
2 grams of magnesium chloride To reduce local discomfort and replace losses
100 mg of procaine HCL To reduce local discomfort
2500 units of heparin To reduce local inflammation of veins
7 grams of ascorbate (Vitamin C) For anti-oxidant properties
2 mEq Potassium To replace losses
840 mg sodium bicarbonate To act as a buffer and reduce discomfort
250mg pantothenic acid For anti-oxidant properties
100mg of thiamine For anti-oxidant properties
100mg of pyridoxine To replace chelation losses
Because chelation therapy may also remove important vitamins and other nutritional elements needed by the body, all patients, including yourself, will be required to take vitamins and nutritional supplements. These supplements will be taken on a daily basis. You will be assigned by chance to receive either high-dose vitamin supplements or high-dose vitamin supplement placebos. Neither you nor the research staff will know to which group you have been assigned. On the day of actual infusion, you will be asked to take these supplements 3-5 hours after the infusion to avoid the possibility of the supplements being removed by the chelation therapy. We will ask you to bring these supplements with you to every infusion visit, to ensure that you are taking them as required.
The high dose vitamin and mineral schedule consists of 3 pills to be taken twice
daily. The pills contain the following components. Please review the list and
notify us if you have an allergy to any of the components:
Total amount you will take High Dose Regimen compared to the (Taken twice daily) recommended Daily Value Vitamin A (as fish liver oil and beta-carotene) 5 times Vitamin C (as calcium ascorbate, magnesium ascorbate and 20 potassium ascorbate)
Vitamin D (as cholecalciferol) ? 3
Vitamin E (as d-alpha tocopheryl succinate and d-alpha 113 /3 tocopheryl acetate)
Vitamin K (as phytonadione) ? 1
2Thiamin (vitamin B) (as thiamin mononitrate) 66 /13 Niacin (as niacinamide and niacin) 10 Vitamin B (as pyridoxine hydrochloride) 25 6
Folate (as folic acid) 2
2Vitamin B (as cyanocobalamin) 16 / 123Biotin Same Pantothenic acid (as d-calcium pantothenate) 40 Calcium (as calcium citrate and calcium ascorbate) ? Iodine (from kelp) Same Magnesium (as magnesium aspartate, magnesium ascorbate 1? and magnesium amino acid chelate)
1Zinc (as zinc amino acid chelate) 1 / 38Selenium (as selenium amino acid chelate) 2 /9 Copper (as copper amino acid chelate) Same Manganese (as manganese amino acid chelate) 4
2Chromium (as chromium polynicotinate) 1 / 3Molybdenum (as molybdenum amino acid chelate) 2
1Potassium (as potassium aspartate and potassium ascorbate) Less than / 8Choline (as choline bitartrate)
There is no Daily Value PABA (as para-amino benzoic acid) established for these Boron (as boron aspartate and boron citrate) supplements. Vanadium (as vanadyl sulfate)
These supplements are taken in up to 6 tablets or capsules daily.
All patients will receive a low-dose set of vitamins, 1 pill to be taken once daily, during the infusion period. This low-dose schedule is presented in the table below. Please review the list for any allergies that you may have:
% Daily Amount Low-Dose Regimen Value (Taken once daily)
Vitamin B6 (as pyridoxine hydrochloride) 25mg 1250%
Zinc (as zinc gluconate) 25mg 167%
Copper (as copper gluconate) 2mg 100%
Manganese (as manganese gluconate) 15mg 750%
Chromium (as chromium picolinate) 50mcg 42%
These supplements, produced by OleoMed S.A., Madrid, Spain, are administered in
an olive oil based gel capsule.
In order to make sure patients and their physicians are “blinded” to which group you have been assigned, all patients assigned to the high-dose vitamin supplement placebo group will be taking pills that are identical to those that the high-dose group is taking.
As part of this study you may be chosen at random to be interviewed by the research staff from the Economics and Quality of Life Center at the Duke Clinical Research Institute. These interviews, done over the phone, will be scheduled at 6 months, 1 year and 2 years after the initial enrollment to the study. The research staff will ask you questions regarding any changes in how you feel, in your ability to perform your daily activities, or in your working status. If you are chosen, the information will allow us to understand the possible effects of chelation and vitamins on the quality and economics of patients’ lives. All of
these data will be analyzed using coded information without your name or other identifiable information that could be made public. The calls will take about 15-25 minutes to complete.
After the 40 infusion visits have been completed, research staff from [INSERT YOUR INSTITUTION’S NAME HERE] will call you every 3 months until the end of
the study to find out how you are doing and whether you have had any heart problems since the last visit or call. During this time it will be important to continue to take your high-dose vitamins. You will also be asked about any
hospitalizations or heart procedures you may have had between study visits. If you have been hospitalized during the follow-up period, it will be necessary for you to sign a release so that we can have access to any medical records related to that hospitalization. In addition, you will be asked to return for a visit each year and at the end of the study. At each visit, you will be asked questions about your medical condition and undergo a simple physical exam.
If you are a woman and are able to become pregnant, you are not eligible to participate in this study.
As a participant in this study you are required to do the following:
- Allow at least 5 hours for each infusion visit.
- Bring your study vitamins in their original packaging (bottle and blister
packs) to each infusion visit. You will receive a new set of vitamins
every 2 months from your Site Coordinator. th- After your 40 infusion, continue to bring your vitamins every 3
months to your Site Coordinator. Your Site Coordinator will provide a
new 3-month supply of vitamins during these visits.
- Take the 3 high-dose pills twice per day during the infusion and follow-
- Take the 1 low-dose capsule once per day, during the infusion period.
- On the day of your infusions, take your assigned vitamins 3-5 hours
after your infusion.
- If someone on the research staff calls you on the telephone, please
answer all their questions.
- Continue taking all other medications for your heart disease and other
conditions as prescribed by your physician.
Risks and Side Effects
This treatment may cause the side effects listed below. However, there may be some side effects that we cannot predict.
EDTA, or ethylenediamine tetraacetate is in the chelation solution. It is approved for use by the FDA as a treatment for lead poisoning but not for coronary artery disease. It binds heavy metals like lead, copper, and iron, and allows them to be excreted in the urine. EDTA rarely may cause allergies, or kidney problems. EDTA also binds to calcium in blood. Symptoms of low blood calcium, such as tingling, muscle cramps, lightheadedness, severe muscular spasms, heart rhythm problems, and low blood pressure may occur with a rapid infusion, and rarely, with a correctly-administered infusion. You will be monitored carefully for these side effects. The infusion will be monitored closely so it does not go in too
quickly, and your blood pressure will be checked before, during, and after the infusion. If your kidney function is not good, you will not be allowed to participate in the study. If your kidney function gets worse during the infusions, then the dose of EDTA will be reduced, or the infusions will be stopped. As part of monitoring your kidney function, you will need to inform your study physician if you are unable to urinate for 12 hours. You may develop flu-like symptoms such as low-grade fevers, sneezing, muscle and joint aches, headaches and watery eyes. These symptoms usually occur 4 to 8 hours after receiving the infusion. These symptoms are usually seen when high doses of EDTA are given, or if the infusion rate is too rapid. Patients with diabetes have been reported to develop low blood sugar during the infusion. For this reason, if you are diabetic, we will ask you to snack before the infusion, and monitor you for symptoms of low blood sugar.
During the infusions, you may experience a “burning-like” sensation at the site of
the infusion, or through the vein. Certain medications (such as magnesium and a local anesthetic) are added to the solution to reduce this discomfort.
EDTA has the ability to remove certain vitamins and minerals that are needed by your body. You will be provided with supplements to be taken by mouth that will replace these elements. Although the risk of removal of these minerals is small, this can cause symptoms such as fatigue, dry skin, tingling sensation in your hands and feet, a skin rash, diarrhea, and constipation. EDTA also may reduce the effectiveness of some of the medications you are taking.
As described earlier, magnesium chloride and potassium chloride are included in the infusion solution. Magnesium and potassium are essential salts that are components of all cells in the body. Potassium can cause burning at the site where the intravenous line is placed. However, there are no other likely side effects expected from the doses to be infused.
Vitamins B1, B6, pantothenic acid, and vitamin C also are included in the infusion solution. These essential vitamins have no significant side effects. However, vitamin C is being used at a higher dose than usual.
Heparin, also included in the infusion solution, is a commonly used blood thinner that is used to prevent clotting of the vein used for the intravenous infusion. The principal side effect of heparin at the doses used in this study is an allergy that could lead to bleeding or blood clots. You will be closely monitored for this, and the heparin will be stopped if an allergy seems to occur.
Procaine, also included in the infusion solution, is a local anesthetic that will prevent stinging or discomfort during the intravenous infusions. The main side effect is the possibility of allergy. Sodium bicarbonate is a naturally occurring
substance that increases the ability of the kidney to excrete impurities. It is included in the infusion solution.
If your heart is weak, you may be at risk of developing fluid in your lungs, swelling in your ankles, or rapid weight gain. This fluid accumulation is also known as heart failure, and is a result of the heart’s inability to tolerate the amount of fluid that will be infused. Your weight will be monitored to make sure you are not accumulating fluid. If your doctor determines that your weight gain is related to the infusions, the infusions will be temporarily stopped. Additionally, your doctor may determine it is necessary to give you a diuretic (water pill) in order to prevent any further fluid from accumulating in your lungs that may lead to shortness of breath. People who already have a history of decreased heart function will be at greater risk. If you have had fluid in your lungs due to a weak heart within the last 6 months, you will not be permitted to participate in the study.
Since chelation therapy is given intravenously, you will have some discomfort at the needle puncture site. There is also a risk of bruising, swelling, and redness developing at the site of the intravenous infusion. Rarely, a serious blood infection may develop that would require antibiotic treatment. It is very important for you to report any pain, swelling, or redness at the site of the needle punctures, as well as any fever or chills, to your doctor or study investigator. You may also experience these discomforts when having your blood drawn.
The oral anti-oxidant vitamin, mineral, and nutrient supplements being provided are well tolerated and have low risks of serious side effects. Beta-carotene, however, one of the supplements used, has been associated with a higher rate of cancer in patients who smoke. Smokers are not eligible to participate in this study, and it is important that you not start smoking while you are participating. You will be informed in a timely manner if new information becomes available that may affect your willingness to continue participation in this study. Finally, there does remain the risk of serious unanticipated side effects that we cannot predict, because this type of study has never been carried out in so many patients.
If you experience one of these side effects, the sponsor (National Institutes of Health) and/or the Data Coordinating Center, (Duke Clinical Research Institute) may need to review your entire medical record.
If you have any questions about the risks or discomforts, contact [INSERT SITE INVESTIGATOR’S NAME AND PHONE NUMBER HERE].
You may or may not receive any medical benefit from your participation in this study. In the future, other people with a similar condition may benefit from the knowledge obtained from this study.
If you choose not to participate in this study, your other cardiac treatments as directed and recommended by your doctor will not be affected. You should continue to use proven standard medicines for heart attack patients whether or not you participate in this research study.
Right to Withdraw
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the study at any time. If you withdraw from the study, no new data about you will be collected for study purposes unless the data concern an adverse event (a bad effect) related to the study. If such an adverse event occurs, we may need to review your entire medical record. All data that have already been collected for study purposes, and any new information about an adverse event related to the study, will be sent to the study sponsor.
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of benefits to which you are entitled, and will not affect your access to health care at [INSERT NAME OF INSTITUTION/HEALTH CARE PROVIDER HERE]. If you do decide to withdraw, we ask that you contact Dr. [INSERT NAME OF SITE INVESTIGATOR HERE] in writing and let [CHOOSE him/her] know that you are withdrawing from the study. [CHOOSE His/Her] mailing address is [INSERT SITE INVESTIGATOR’S ADDRESS HERE].
Your doctor may ask you to leave this study if he/she feels it is appropriate or necessary. Your doctor will notify you if this should occur. This in no way will affect your continued medical care and treatment by your physician. Should you decide to discontinue your study participation early, you are asked to contact [INSERT SITE INVESTIGATOR’S NAME HERE] to arrange for final study visit
procedures. In addition, the investigator, the sponsor, or the FDA, without regard to your consent, may terminate your participation in this study if either party believes it to be in your best interest. Such conditions may include, but are not limited to, a serious adverse reaction, a worsening of your condition, or lack of cooperation on your part.
A Data Safety and Monitoring Board, an independent group of experts, will be
the information from this research throughout the study. We will tell you about
information from this or other studies that may affect your health, welfare, or willingness to stay in this study.
You or your insurance company will not be charged for the study treatments or for tests required by the study. All the study medications are provided free of charge to participating research subjects.
Should you have a complication of chelation therapy that requires medication or hospitalization, the study and/or its researchers will be unable to pay for those costs, and you and/or your insurance company will be responsible for the costs resulting from the complication.
You will not be paid to participate in this study.
If you do not sign this consent form, you will continue to receive care from your regular physician, but not as a part of this study.
Study records that identify you will be kept confidential as required by law. Federal Privacy Regulations provide safeguards for privacy, security, and authorized access. Except as previously addressed in this consent, you will not be identified by name, social security number, address, telephone number, or any other direct personal identifier in study records disclosed outside of [INSERT SITE INSTITUTION NAME HERE]. For records disclosed outside of [INSERT SITE INSTITUTION NAME HERE], you will be assigned a unique code number. The key to the code will be kept in a locked file at the Duke Clinical Research Institute (DCRI).
As part of the study, Dr.[INSERT SITE INVESTIGATOR'S NAME HERE] and [CHOOSE HIS/HER] study team will report the results of your study-related laboratory tests to those named below. These test results will be reported to the TACT Clinical Coordinating Center, TACT Clinical Events Committee, Accu-Care Pharmacy Services, and OmniComm Systems.
Your records may be reviewed in order to meet federal or state regulations. Reviewers may include, for example, representatives from the Food and Drug Administration, representatives of [INSERT NAME OF PI HERE], the Institutional Review Board, DCRI associates, NCCAM and NHLBI. If your research record is